Reaction of Melatonin and Related Indoles With Hydroxyl Radicals: EPR and Spin Trapping Investigations

It has been suggested that the indole hormone melatonin (N-acetyl-5-methoxytryptamine, MLT) is an important natural antioxidant and free radical scavenger [J. Pineal Res., 14: 51; 1993]. In the present work we determined the rate constants, kr, for scavenging ˙OH radicals by melatonin, 5-methoxytryptamine (5-MeO-T), 5-hydroxytryptamine (serotonin, 5-OH-T), 6-chloromelatonin (6-Cl-MLT), 6-hydroxymelatonin (6-OH-MLT), and kynurenine (KN) in aqueous solutions. Hydroxyl radicals were generated using a Fenton reaction in the presence of the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO), which competed with the indoles for the radicals. It was found that MLT reacts with ˙OH with kr = 2.7 × 1010 M−1 s−1. Other indoles and KN reacted with ˙OH radicals with similarly high rates (kr > 1010 M−1 s−1). In contrast to nonhydroxylated indoles (MLT, 6-Cl-MLT, and 5-MeO-T), hydroxylated indoles (5-OH-T and 6-OH-MLT) may function both as ˙OH promoters and ˙OH scavengers. The melatonin precursor serotonin promoted the generation of ˙OH radicals in the presence of ferric iron and H2O2, and the melatonin metabolite 6-hydroxymelatonin generated large quantities of ˙OH radicals in aerated solutions containing Fe3+ ion, even in the absence of externally added hydrogen peroxide. These reactions may be relevant to the biological action of these physiologically important indolic compounds.